Clinical Exploration Study of YOLT-203 in the Treatment of Type 1 Primary Hyperoxaluria (PH1)

NCT06511349 | Recruiting Early Phase 1

• 1 other identifier: PH1-YOLT-203-001
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-arm, open-label, single-dose, dose-escalation, and dose-expansion trial, aiming to assess the safety and tolerability of YOLT-203 in Chinese patients with Primary Hyperoxaluria Type 1 (PH1), and to preliminarily evaluate the effect of a single dose of YOLT-203 on plasma oxalate levels. In this study, the maximum duration of the screening period is 60 days, with the treatment day being Day 1 (D1), and the safety follow-up period extending to the 52nd week after dosing. Additionally, in the dose-escalation phase, after the first dose cohort, investigators will conduct a comprehensive evaluation based on safety, pharmacokinetic (PK), and pharmacodynamic (PD) data, and following discussion at the Safety Review Committee (SRC) meeting, subjects may voluntarily receive a second administration of the study drug at an effective dose level. After the completion of the main study, subjects will undergo long-term follow-up. In accordance with the requirements of the "Technical Guidance for Clinical Research on Long-term Follow-up of Gene Therapy Products (Trial)" issued by the Center for Drug Evaluation (CDE), long-term follow-up will be conducted for up to 15 years after dosing.

Conditions

Type 1 Primary Hyperoxaluria

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  through week 52

Secondary Outcomes (8)

• pharmacokinetics of YOLT-203

  through Day 14

• pharmacokinetics of YOLT-203

  through Day 14

• pharmacokinetics of YOLT-203

  through Day 28

• pharmacokinetics of YOLT-203

  through Day 28

• pharmacodynamics

  through week 52

Study Arms (1)

TOLT-203

EXPERIMENTAL

Drug: YOLT-203

Interventions

YOLT-203 DRUG

The IP is administered intravenously at the predetermined dose.

TOLT-203

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The age is ≥ 2 years old at the time of signing the informed consent.
• Have AGXT gene mutations and be diagnosed with primary hyperoxaluria (PH1); eGFR ≥ 30 ml/min/1.73m2.
• At least 2 times of 24-hour urinary oxalate excretion ≥ 0.7 mmol/1.73m2/day or the ratio of urinary oxalate to creatinine in a single urine collection must be higher than the upper limit of normal (ULN) for the corresponding age.
• If treated with vitamin B6, the treatment has been stable for 90 days before enrollment in the study and is willing to maintain the stable treatment plan unchanged during the study.
• The patient himself/herself or the guardian voluntarily signs the informed consent.

You may not qualify if:

• The investigator judges that there is clinical evidence of systemic extra-renal oxalate deposition.
• Have any of the following laboratory parameter assessment results at screening:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 x the upper limit of normal (ULN).
• Total bilirubin \> 1.5 x ULN. If the increase in total bilirubin is caused by diagnosed Gilbert's syndrome and the total bilirubin \< 2 x ULN, it is eligible.
• International normalized ratio (INR) \> 1.5 (Patients on oral anticoagulants \[such as warfarin\] and with INR \< 3.5 will be allowed to participate).
• Known to have active human immunodeficiency virus (HIV) infection; or have evidence of current or chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection.
• The estimated glomerular filtration rate (GFR) at screening is less than 30 mL/min/1.73m² (For patients ≥ 18 years old, it will be calculated according to the Modification of Diet in Renal Disease \[MDRD\] formula; for patients \< 18 years old, it will be calculated according to the Schwartz bedside formula). See the attachment.
• Have received an investigational drug within the last 30 days or 5 half-lives (whichever is longer) before the first administration of the study drug, or have participated in the follow-up of another clinical study before randomization.
• Have a history of kidney or liver transplantation.
• According to the investigator's opinion, have other medical conditions or comorbidities that may interfere with study compliance or data interpretation.
• Have a history of multiple drug allergies or allergic reaction history to oligonucleotides or LNP.
• Have a history of subcutaneous injection intolerance.
• Unwilling to comply with contraceptive requirements throughout the study participation period until 6 months after the end of the main study trial.
• Female patients are pregnant, planning to become pregnant or breastfeeding.
• Unwilling or unable to limit alcohol consumption throughout the study. Alcohol consumption during the study exceeds 2 units per day (1 unit: approximately 125 ml of wine = approximately 29 ml of spirits = approximately 284 ml of beer, will be excluded.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, 200127, China

RECRUITING

MeSH Terms

Conditions

Primary hyperoxaluria type 1

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 0.3mg/kg,0.45mg/kg,0.6mg/kg,35mg

Study Record Dates

• First Submitted: July 4, 2024
• First Posted: July 19, 2024
• Study Start: July 15, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 16, 2025

Record last verified: 2025-05

Locations

CN (1)